The EWAS Catalog: a database of epigenome-wide association studies

Battram, Thomas; Yousefi, Paul; Crawford, Gemma; Prince, Claire; Babaei, Mahsa Sheikhali; Sharp, Gemma C; Hatcher, Charlie; Vega‐Salas, María Jesús; Khodabakhsh, Sahar; Whitehurst, Oliver; Langdon, Ryan; Mahoney, Luke; Elliott, Hannah R; Mancano, Giulia; Lee, Matthew A.; Watkins, Sarah; Lay, Abigail C; Hemani, Gibran; Gaunt, Tom R.; Relton, Caroline L; Staley, James R; Suderman, Matthew

doi:10.12688/wellcomeopenres.17598.2

Cited by 125 publications

(102 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Details are provided in the supplementary methods. Additionally, we compared our findings to previous studies using the publicly available EWAS catalog [ 57 ] and conducted further searches on PubMed.…”

Section: Methodsmentioning

confidence: 99%

DNA methylation as a potential mediator of the association between prenatal tobacco and alcohol exposure and child neurodevelopment in a South African birth cohort

et al. 2022

View full text Add to dashboard Cite

Prenatal tobacco exposure (PTE) and prenatal alcohol exposure (PAE) have been associated with an increased risk of delayed neurodevelopment in children as well as differential newborn DNA methylation (DNAm). However, the biological mechanisms connecting PTE and PAE, DNAm, and neurodevelopment are largely unknown. Here we aim to determine whether differential DNAm mediates the association between PTE and PAE and neurodevelopment at 6 (N = 112) and 24 months (N = 184) in children from the South African Drakenstein Child Health Study. PTE and PAE were assessed antenatally using urine cotinine measurements and the ASSIST questionnaire, respectively. Cord blood DNAm was measured using the EPIC and 450 K BeadChips. Neurodevelopment (cognitive, language, motor, adaptive behavior, socioemotional) was measured using the Bayley Scales of Infant and Toddler Development, Third Edition. We constructed methylation risk scores (MRS) for PTE and PAE and conducted causal mediation analysis (CMA) with these MRS as mediators. Next, we conducted a high-dimensional mediation analysis to identify individual CpG sites as potential mediators, followed by a CMA to estimate the average causal mediation effects (ACME) and total effect (TE). PTE and PAE were associated with neurodevelopment at 6 but not at 24 months. PTE MRS reached a prediction accuracy (R2) of 0.23 but did not significantly mediate the association between PTE and neurodevelopment. PAE MRS was not predictive of PAE (R2 = 0.006). For PTE, 31 CpG sites and eight CpG sites were identified as significant mediators (ACME and TE P < 0.05) for the cognitive and motor domains at 6 months, respectively. For PAE, 16 CpG sites and 1 CpG site were significant mediators for the motor and adaptive behavior domains at 6 months, respectively. Several of the associated genes, including MAD1L1, CAMTA1, and ALDH1A2 have been implicated in neurodevelopmental delay, suggesting that differential DNAm may partly explain the biological mechanisms underlying the relationship between PTE and PAE and child neurodevelopment.

show abstract

Section: Methodsmentioning

confidence: 99%

DNA methylation as a potential mediator of the association between prenatal tobacco and alcohol exposure and child neurodevelopment in a South African birth cohort

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/ijms23147557/s1. References [94][95][96] are cited in the supplementary materials.…”

Section: Supplementary Materialsmentioning

confidence: 99%

“…The following supporting information can be downloaded at: . References [ 94 , 95 , 96 ] are cited in the supplementary materials.…”

mentioning

confidence: 99%

Large-Scale Multi-Omics Studies Provide New Insights into Blood Pressure Regulation

Kamali

Keaton

Javanmard

et al. 2022

IJMS

View full text Add to dashboard Cite

Recent genome-wide association studies uncovered part of blood pressure’s heritability. However, there is still a vast gap between genetics and biology that needs to be bridged. Here, we followed up blood pressure genome-wide summary statistics of over 750,000 individuals, leveraging comprehensive epigenomic and transcriptomic data from blood with a follow-up in cardiovascular tissues to prioritise likely causal genes and underlying blood pressure mechanisms. We first prioritised genes based on coding consequences, multilayer molecular associations, blood pressure-associated expression levels, and coregulation evidence. Next, we followed up the prioritised genes in multilayer studies of genomics, epigenomics, and transcriptomics, functional enrichment, and their potential suitability as drug targets. Our analyses yielded 1880 likely causal genes for blood pressure, tens of which are targets of the available licensed drugs. We identified 34 novel genes for blood pressure, supported by more than one source of biological evidence. Twenty-eight (82%) of these new genes were successfully replicated by transcriptome-wide association analyses in a large independent cohort (n = ~220,000). We also found a substantial mediating role for epigenetic regulation of the prioritised genes. Our results provide new insights into genetic regulation of blood pressure in terms of likely causal genes and involved biological pathways offering opportunities for future translation into clinical practice.

show abstract

“…We report the relative contribution of genetic and environmental sources of variance in ethnicity-associated DNA methylation and also explore sources of environmental variation. We finally assess whether ethnicity-associated CpG sites are functionally implicated in biological pathways (using publicly available databases) or disease endpoints or risk factors captured by the EWAS Catalog [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

Characterisation of ethnic differences in DNA methylation between UK-resident South Asians and Europeans

et al. 2022

Self Cite

View full text Add to dashboard Cite

Ethnic differences in non-communicable disease risk have been described between individuals of South Asian and European ethnicity that are only partially explained by genetics and other known risk factors. DNA methylation is one underexplored mechanism that may explain differences in disease risk. Currently, there is little knowledge of how DNA methylation varies between South Asian and European ethnicities. This study characterised differences in blood DNA methylation between individuals of self-reported European and South Asian ethnicity from two UK-based cohorts: Southall and Brent Revisited and Born in Bradford. DNA methylation differences between ethnicities were widespread throughout the genome (n = 16,433 CpG sites, 3.4% sites tested). Specifically, 76% of associations were attributable to ethnic differences in cell composition with fewer effects attributable to smoking and genetic variation. Ethnicity-associated CpG sites were enriched for EWAS Catalog phenotypes including metabolites. This work highlights the need to consider ethnic diversity in epigenetic research.

show abstract

The EWAS Catalog: a database of epigenome-wide association studies

Cited by 125 publications

References 13 publications

DNA methylation as a potential mediator of the association between prenatal tobacco and alcohol exposure and child neurodevelopment in a South African birth cohort

DNA methylation as a potential mediator of the association between prenatal tobacco and alcohol exposure and child neurodevelopment in a South African birth cohort

Large-Scale Multi-Omics Studies Provide New Insights into Blood Pressure Regulation

Characterisation of ethnic differences in DNA methylation between UK-resident South Asians and Europeans

Contact Info

Product

Resources

About